Effects of long‐term treatment with oxytocin in chronic constipation; a double blind, placebo‐controlled pilot trial

Ohlsson, Bodil; Truedsson, Mikael; Bengtsson, Mariette; Torstenson, Richard; Sjölund, K.; Bjõrnsson, Einar; Simrén, Magnus

doi:10.1111/j.1365-2982.2005.00679.x

Cited by 74 publications

(69 citation statements)

References 37 publications

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“…For instance oxytocin in placebo controlled trials was shown to reduce the severity of headache and colonic visceral perception in irritable bowel syndrome (Louvel et al, 1996) but produced no beneficial effect in fibromyalgia (Mameli et al, 2014) or pain in chronic constipation (Ohlsson et al, 2005). While oxytocin has been reported to reduce pain and unpleasantness in the cold pressor test and acute laser evoked thermal pain (Paloyelis et al, 2016b) other experimental pain models have not shown a clear anti-nociceptive effect (Kessner et al, 2013;Zunhammer et al, 2015).…”

Section: The Analgesic Effects Of Oxytocinmentioning

confidence: 99%

C-tactile afferents: Cutaneous mediators of oxytocin release during affiliative tactile interactions?

et al. 2017

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Low intensity, non-noxious, stimulation of cutaneous somatosensory nerves has been shown to trigger oxytocin release and is associated with increased social motivation, plus reduced physiological and behavioural reactivity to stressors. However, to date, little attention has been paid to the specific nature of the mechanosensory nerves which mediate these effects. In recent years, the neuroscientific study of human skin nerves (microneurography studies on single peripheral nerve fibres) has led to the identification and characterisation of a class of touch sensitive nerve fibres named C-Tactile afferents. Neither itch nor pain receptive, these unmyelinated, low threshold mechanoreceptors, found only in hairy skin, respond optimally to low force/velocity stroking touch. Notably, the speed of stroking which c-tactile afferents fire most strongly to is also that which people perceive to be most pleasant. The social touch hypothesis posits that this system of nerves has evolved in mammals to signal the rewarding value of physical contact in nurturing and social interactions. In support of this hypothesis, in this paper we review the evidence that cutaneous stimulation directly targeted to optimally activate c-tactile afferents reduces physiological arousal, carries a positive affective value and, under healthy conditions, inhibits responses to painful stimuli. These effects mirror those, we also review, which have been reported following endogenous release and exogenous administration of oxytocin. Taken together this evidence suggests c-tactile afferent stimulation may mediate oxytocin release during affiliative tactile interactions.

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Section: The Analgesic Effects Of Oxytocinmentioning

confidence: 99%

C-tactile afferents: Cutaneous mediators of oxytocin release during affiliative tactile interactions?

et al. 2017

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“…Recent studies have shown that OT function (and that of the closely related hormone vasopressin) is impaired in brain disorders associated with social dysfunction such as autism, social anxiety, stress and schizophrenia, triggering an explosion of interest in the use of OT for treatment of mental conditions 5,6 . OT receptors have also attracted attention for their role in memory 7 , breast cancer tumour growth 8 and visceral pain 9,10 . Nasal administration of OT reduces abdominal pain and discomfort in patients with chronic idiopathic constipation 9 , whereas continuous intravenous OT significantly increases thresholds for visceral perception in patients with Irritable Bowel Syndrome (IBS) 10 .…”

mentioning

confidence: 99%

“…OT receptors have also attracted attention for their role in memory 7 , breast cancer tumour growth 8 and visceral pain 9,10 . Nasal administration of OT reduces abdominal pain and discomfort in patients with chronic idiopathic constipation 9 , whereas continuous intravenous OT significantly increases thresholds for visceral perception in patients with Irritable Bowel Syndrome (IBS) 10 . The mechanisms underlying these effects remain unclear and are important to determine as chronic abdominal pain represents a major clinical problem, with IBS alone affecting B11% of the Western population 11 .…”

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confidence: 99%

Selenoether oxytocin analogues have analgesic properties in a mouse model of chronic abdominal pain

et al. 2014

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Poor oral availability and susceptibility to reduction and protease degradation is a major hurdle in peptide drug development. However, drugable receptors in the gut present an attractive niche for peptide therapeutics. Here we demonstrate, in a mouse model of chronic abdominal pain, that oxytocin receptors are significantly upregulated in nociceptors innervating the colon. Correspondingly, we develop chemical strategies to engineer non-reducible and therefore more stable oxytocin analogues. Chemoselective selenide macrocyclization yields stabilized analogues equipotent to native oxytocin. Ultra-high-field nuclear magnetic resonance structural analysis of native oxytocin and the seleno-oxytocin derivatives reveals that oxytocin has a pre-organized structure in solution, in marked contrast to earlier X-ray crystallography studies. Finally, we show that these seleno-oxytocin analogues potently inhibit colonic nociceptors both in vitro and in vivo in mice with chronic visceral hypersensitivity. Our findings have potentially important implications for clinical use of oxytocin analogues and disulphide-rich peptides in general.

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“…In recent years, more evidence has indicated that OT may play a role in regulation of the gastrointestinal (GI) functions such as motility, sensation (13,18), and immune response to inflammation (4,10). Exogenous OT influences the GI motility, although the reports are diverse because of the differences of species, methods, and area of the gut (18,24).…”

mentioning

confidence: 99%

Estradiol upregulates the expression of oxytocin receptor in colon in rats

Feng

Qin²,

Wang³

et al. 2009

American Journal of Physiology-Endocrinology and Metabolism

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The study was designed to investigate the effect of estradiol on the excitatory effect of oxytocin (OT) on colon motility. Female Wistar rats were used, and some of them were ovariectomized (OVX) and treated with vehicle or estradiol (E2). A plastic balloon made of condom was inserted into colon to monitor the change of colonic pressure in vivo. Longitudinal muscle strips of distal colon were prepared to monitor the spontaneous contraction of colon in vitro. Expression of OT receptor (OTR) was investigated by Western blot analysis. Expression of OTR mRNA was detected by RT-PCR. Immunohistochemistry was used to locate OTR. In OVX rats, pretreatment of E2 (4 -100 g/kg sc) dose-dependently increased the excitatory effect of OT on colon motility both in vivo and in vitro and increased the expression of OTR and OTR mRNA in colon. Systemic administration of OT excited the colon motility in vivo in rats at perioda of proestrus and estrus but did not influence it at diestrus period, when the concentration of plasma E2 was lowest in the estrous cycle. Pretreatment of atosiban, the specific OTR antagonist, and TTX, the blocker of voltage-dependent sodium channel on nerve fiber, attenuated the excitatory effect of OT on colon motility. OTR was located in myenteric plexus of colon. These results suggested that E2 increased the excitatory effect of OT on colon motility by upregulating the expression of OTR in myenteric plexus.colon; motility OXYTOCIN (OT) has been traditionally regarded as a hormone that is involved in parturition and milk ejection. In recent years, more evidence has indicated that OT may play a role in regulation of the gastrointestinal (GI) functions such as motility, sensation (13, 18), and immune response to inflammation (4, 10). Exogenous OT influences the GI motility, although the reports are diverse because of the differences of species, methods, and area of the gut (18, 24). It has been suggested that the effect of OT on GI motility might be physiological. OT is released in response to a fatty meal in women (16). Systemic administration of atosiban, the antagonist of OT receptor (OTR), inhibited the spontaneous contraction of gallbladder in rabbits (12) and gastric emptying in humans (16). It has been well established that mRNA for OT and its receptor can be found throughout the human GI tract (15), but the cell types that express OTR were undetectable in human gut by indirect immunofluorescence (19).In women, colonic dysmotility is very common, and bowel function changes during the reproductive cycle. Although the fluctuation of steroid hormones, especially estradiol (E 2 ) and progesterone, were believed to be the major reason, the mechanism has not been clearly illustrated. Steroid hormones regulate the activity of OTR via both genomic and nongenomic pathways (26). E 2 induced the mRNA expression of the OTR and increased the OTR density on the membranes of the uterine smooth muscle and central nervous system (8, 21). The recent study of our group also indicated that the pretreatment of E 2 increas...

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Effects of long‐term treatment with oxytocin in chronic constipation; a double blind, placebo‐controlled pilot trial

Abstract: Nasal administration of oxytocin had no significant advantage over placebo concerning an effect on constipation. However, it seems to have a positive effect on abdominal pain and discomfort and depressed mood. These findings should be further explored.

Cited by 74 publications

References 37 publications

C-tactile afferents: Cutaneous mediators of oxytocin release during affiliative tactile interactions?

C-tactile afferents: Cutaneous mediators of oxytocin release during affiliative tactile interactions?

Selenoether oxytocin analogues have analgesic properties in a mouse model of chronic abdominal pain

Estradiol upregulates the expression of oxytocin receptor in colon in rats

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